Subunit Composition of Synaptic AMPA Receptors Revealed by a Single-Cell Genetic Approach
The precise subunit composition of synaptic ionotropic receptors in the brain is poorly understood. This information is of particular importance with regard to AMPA-type glutamate receptors, the multimeric complexes assembled from GluA1-A4 subunits, as the trafficking of these receptors into and out...
Gespeichert in:
| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2009-04, Vol.62 (2), p.254-268 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 268 |
|---|---|
| container_issue | 2 |
| container_start_page | 254 |
| container_title | Neuron (Cambridge, Mass.) |
| container_volume | 62 |
| creator | Lu, Wei Shi, Yun Jackson, Alexander C. Bjorgan, Kirsten During, Matthew J. Sprengel, Rolf Seeburg, Peter H. Nicoll, Roger A. |
| description | The precise subunit composition of synaptic ionotropic receptors in the brain is poorly understood. This information is of particular importance with regard to AMPA-type glutamate receptors, the multimeric complexes assembled from GluA1-A4 subunits, as the trafficking of these receptors into and out of synapses is proposed to depend upon the subunit composition of the receptor. We report a molecular quantification of synaptic AMPA receptors (AMPARs) by employing a single-cell genetic approach coupled with electrophysiology in hippocampal CA1 pyramidal neurons. In contrast to prevailing views, we find that GluA1A2 heteromers are the dominant AMPARs at CA1 cell synapses (∼80%). In cells lacking GluA1, -A2, and -A3, synapses are devoid of AMPARs, yet synaptic NMDA receptors (NMDARs) and dendritic morphology remain unchanged. These data demonstrate a functional dissociation of AMPARs from trafficking of NMDARs and neuronal morphogenesis. This study provides a functional quantification of the subunit composition of AMPARs in the CNS and suggests novel roles for AMPAR subunits in receptor trafficking. |
| doi_str_mv | 10.1016/j.neuron.2009.02.027 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3632349</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0896627309002554</els_id><sourcerecordid>3235467691</sourcerecordid><originalsourceid>FETCH-LOGICAL-c555t-3f37feacac5f96319d243d4efea5da008eee9adfbde3194d35ee6cdc17a0e0153</originalsourceid><addsrcrecordid>eNp9UdGKEzEUDaK4dfUPRAKCb1NvJpPJ5kUoRVdhl12sPvgU0uTObso0GZOZQv_e1BbX9UG4kJB77rk55xDymsGcAWvfb-YBpxTDvAZQc6hLySdkxkDJqmFKPSUzuFBt1daSn5EXOW8AWCMUe07OmGpA1RJm5MdqWk_Bj3QZt0PMfvQx0NjR1T6YYfSWLq5vF_QrWhzGmHK57dD06Oh6Tw1d-XDXY7XEvqeXGPD3wDCkaOz9S_KsM33GV6fznHz_9PHb8nN1dXP5Zbm4qqwQYqx4x2WHxhorOtVyplzdcNdgeRPOAFwgojKuWzsszcZxgdhaZ5k0gMAEPycfjrzDtN6isxjGZHo9JL81aa-j8fpxJ_h7fRd3mre85o0qBO9OBCn-nDCPeuuzLZJMwDhl3coaeHG1AN_-A9zEKYUiTjMBXMpiKiuo5oiyKeacsPvzFQb6kJze6GNy-pCchrrUgfzN3zIehk5RPejEYubOY9LZegwWnU9oR-2i__-GX2nrrhE</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1503774091</pqid></control><display><type>article</type><title>Subunit Composition of Synaptic AMPA Receptors Revealed by a Single-Cell Genetic Approach</title><source>MEDLINE</source><source>Cell Press Free Archives</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Access via ScienceDirect (Elsevier)</source><creator>Lu, Wei ; Shi, Yun ; Jackson, Alexander C. ; Bjorgan, Kirsten ; During, Matthew J. ; Sprengel, Rolf ; Seeburg, Peter H. ; Nicoll, Roger A.</creator><creatorcontrib>Lu, Wei ; Shi, Yun ; Jackson, Alexander C. ; Bjorgan, Kirsten ; During, Matthew J. ; Sprengel, Rolf ; Seeburg, Peter H. ; Nicoll, Roger A.</creatorcontrib><description>The precise subunit composition of synaptic ionotropic receptors in the brain is poorly understood. This information is of particular importance with regard to AMPA-type glutamate receptors, the multimeric complexes assembled from GluA1-A4 subunits, as the trafficking of these receptors into and out of synapses is proposed to depend upon the subunit composition of the receptor. We report a molecular quantification of synaptic AMPA receptors (AMPARs) by employing a single-cell genetic approach coupled with electrophysiology in hippocampal CA1 pyramidal neurons. In contrast to prevailing views, we find that GluA1A2 heteromers are the dominant AMPARs at CA1 cell synapses (∼80%). In cells lacking GluA1, -A2, and -A3, synapses are devoid of AMPARs, yet synaptic NMDA receptors (NMDARs) and dendritic morphology remain unchanged. These data demonstrate a functional dissociation of AMPARs from trafficking of NMDARs and neuronal morphogenesis. This study provides a functional quantification of the subunit composition of AMPARs in the CNS and suggests novel roles for AMPAR subunits in receptor trafficking.</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/j.neuron.2009.02.027</identifier><identifier>PMID: 19409270</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Animals, Newborn ; Biophysics ; Brain research ; Electric Stimulation ; Excitatory Amino Acid Antagonists - pharmacology ; Excitatory Postsynaptic Potentials - drug effects ; Excitatory Postsynaptic Potentials - physiology ; Glutamic Acid - pharmacology ; Green Fluorescent Proteins - genetics ; Hippocampus - cytology ; In Vitro Techniques ; Membrane Potentials - drug effects ; Membrane Potentials - genetics ; Membrane Potentials - physiology ; Mice ; Mice, Transgenic ; Models, Neurological ; MOLNEURO ; Neurons ; Neurons - drug effects ; Neurons - physiology ; Patch-Clamp Techniques ; Polyamines ; Protein Subunits - genetics ; Protein Subunits - metabolism ; Protein Transport - drug effects ; Receptors, AMPA - deficiency ; Receptors, AMPA - genetics ; Receptors, AMPA - metabolism ; Receptors, Neurotransmitter - genetics ; Receptors, Neurotransmitter - metabolism ; Rodents ; SIGNALING</subject><ispartof>Neuron (Cambridge, Mass.), 2009-04, Vol.62 (2), p.254-268</ispartof><rights>2009 Elsevier Inc.</rights><rights>Copyright Elsevier Limited Apr 30, 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c555t-3f37feacac5f96319d243d4efea5da008eee9adfbde3194d35ee6cdc17a0e0153</citedby><cites>FETCH-LOGICAL-c555t-3f37feacac5f96319d243d4efea5da008eee9adfbde3194d35ee6cdc17a0e0153</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neuron.2009.02.027$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,3551,27928,27929,45999</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19409270$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Wei</creatorcontrib><creatorcontrib>Shi, Yun</creatorcontrib><creatorcontrib>Jackson, Alexander C.</creatorcontrib><creatorcontrib>Bjorgan, Kirsten</creatorcontrib><creatorcontrib>During, Matthew J.</creatorcontrib><creatorcontrib>Sprengel, Rolf</creatorcontrib><creatorcontrib>Seeburg, Peter H.</creatorcontrib><creatorcontrib>Nicoll, Roger A.</creatorcontrib><title>Subunit Composition of Synaptic AMPA Receptors Revealed by a Single-Cell Genetic Approach</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>The precise subunit composition of synaptic ionotropic receptors in the brain is poorly understood. This information is of particular importance with regard to AMPA-type glutamate receptors, the multimeric complexes assembled from GluA1-A4 subunits, as the trafficking of these receptors into and out of synapses is proposed to depend upon the subunit composition of the receptor. We report a molecular quantification of synaptic AMPA receptors (AMPARs) by employing a single-cell genetic approach coupled with electrophysiology in hippocampal CA1 pyramidal neurons. In contrast to prevailing views, we find that GluA1A2 heteromers are the dominant AMPARs at CA1 cell synapses (∼80%). In cells lacking GluA1, -A2, and -A3, synapses are devoid of AMPARs, yet synaptic NMDA receptors (NMDARs) and dendritic morphology remain unchanged. These data demonstrate a functional dissociation of AMPARs from trafficking of NMDARs and neuronal morphogenesis. This study provides a functional quantification of the subunit composition of AMPARs in the CNS and suggests novel roles for AMPAR subunits in receptor trafficking.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Biophysics</subject><subject>Brain research</subject><subject>Electric Stimulation</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Excitatory Postsynaptic Potentials - drug effects</subject><subject>Excitatory Postsynaptic Potentials - physiology</subject><subject>Glutamic Acid - pharmacology</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Hippocampus - cytology</subject><subject>In Vitro Techniques</subject><subject>Membrane Potentials - drug effects</subject><subject>Membrane Potentials - genetics</subject><subject>Membrane Potentials - physiology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Models, Neurological</subject><subject>MOLNEURO</subject><subject>Neurons</subject><subject>Neurons - drug effects</subject><subject>Neurons - physiology</subject><subject>Patch-Clamp Techniques</subject><subject>Polyamines</subject><subject>Protein Subunits - genetics</subject><subject>Protein Subunits - metabolism</subject><subject>Protein Transport - drug effects</subject><subject>Receptors, AMPA - deficiency</subject><subject>Receptors, AMPA - genetics</subject><subject>Receptors, AMPA - metabolism</subject><subject>Receptors, Neurotransmitter - genetics</subject><subject>Receptors, Neurotransmitter - metabolism</subject><subject>Rodents</subject><subject>SIGNALING</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UdGKEzEUDaK4dfUPRAKCb1NvJpPJ5kUoRVdhl12sPvgU0uTObso0GZOZQv_e1BbX9UG4kJB77rk55xDymsGcAWvfb-YBpxTDvAZQc6hLySdkxkDJqmFKPSUzuFBt1daSn5EXOW8AWCMUe07OmGpA1RJm5MdqWk_Bj3QZt0PMfvQx0NjR1T6YYfSWLq5vF_QrWhzGmHK57dD06Oh6Tw1d-XDXY7XEvqeXGPD3wDCkaOz9S_KsM33GV6fznHz_9PHb8nN1dXP5Zbm4qqwQYqx4x2WHxhorOtVyplzdcNdgeRPOAFwgojKuWzsszcZxgdhaZ5k0gMAEPycfjrzDtN6isxjGZHo9JL81aa-j8fpxJ_h7fRd3mre85o0qBO9OBCn-nDCPeuuzLZJMwDhl3coaeHG1AN_-A9zEKYUiTjMBXMpiKiuo5oiyKeacsPvzFQb6kJze6GNy-pCchrrUgfzN3zIehk5RPejEYubOY9LZegwWnU9oR-2i__-GX2nrrhE</recordid><startdate>20090430</startdate><enddate>20090430</enddate><creator>Lu, Wei</creator><creator>Shi, Yun</creator><creator>Jackson, Alexander C.</creator><creator>Bjorgan, Kirsten</creator><creator>During, Matthew J.</creator><creator>Sprengel, Rolf</creator><creator>Seeburg, Peter H.</creator><creator>Nicoll, Roger A.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090430</creationdate><title>Subunit Composition of Synaptic AMPA Receptors Revealed by a Single-Cell Genetic Approach</title><author>Lu, Wei ; Shi, Yun ; Jackson, Alexander C. ; Bjorgan, Kirsten ; During, Matthew J. ; Sprengel, Rolf ; Seeburg, Peter H. ; Nicoll, Roger A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c555t-3f37feacac5f96319d243d4efea5da008eee9adfbde3194d35ee6cdc17a0e0153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Biophysics</topic><topic>Brain research</topic><topic>Electric Stimulation</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Excitatory Postsynaptic Potentials - drug effects</topic><topic>Excitatory Postsynaptic Potentials - physiology</topic><topic>Glutamic Acid - pharmacology</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Hippocampus - cytology</topic><topic>In Vitro Techniques</topic><topic>Membrane Potentials - drug effects</topic><topic>Membrane Potentials - genetics</topic><topic>Membrane Potentials - physiology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Models, Neurological</topic><topic>MOLNEURO</topic><topic>Neurons</topic><topic>Neurons - drug effects</topic><topic>Neurons - physiology</topic><topic>Patch-Clamp Techniques</topic><topic>Polyamines</topic><topic>Protein Subunits - genetics</topic><topic>Protein Subunits - metabolism</topic><topic>Protein Transport - drug effects</topic><topic>Receptors, AMPA - deficiency</topic><topic>Receptors, AMPA - genetics</topic><topic>Receptors, AMPA - metabolism</topic><topic>Receptors, Neurotransmitter - genetics</topic><topic>Receptors, Neurotransmitter - metabolism</topic><topic>Rodents</topic><topic>SIGNALING</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Wei</creatorcontrib><creatorcontrib>Shi, Yun</creatorcontrib><creatorcontrib>Jackson, Alexander C.</creatorcontrib><creatorcontrib>Bjorgan, Kirsten</creatorcontrib><creatorcontrib>During, Matthew J.</creatorcontrib><creatorcontrib>Sprengel, Rolf</creatorcontrib><creatorcontrib>Seeburg, Peter H.</creatorcontrib><creatorcontrib>Nicoll, Roger A.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuron (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Wei</au><au>Shi, Yun</au><au>Jackson, Alexander C.</au><au>Bjorgan, Kirsten</au><au>During, Matthew J.</au><au>Sprengel, Rolf</au><au>Seeburg, Peter H.</au><au>Nicoll, Roger A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Subunit Composition of Synaptic AMPA Receptors Revealed by a Single-Cell Genetic Approach</atitle><jtitle>Neuron (Cambridge, Mass.)</jtitle><addtitle>Neuron</addtitle><date>2009-04-30</date><risdate>2009</risdate><volume>62</volume><issue>2</issue><spage>254</spage><epage>268</epage><pages>254-268</pages><issn>0896-6273</issn><eissn>1097-4199</eissn><abstract>The precise subunit composition of synaptic ionotropic receptors in the brain is poorly understood. This information is of particular importance with regard to AMPA-type glutamate receptors, the multimeric complexes assembled from GluA1-A4 subunits, as the trafficking of these receptors into and out of synapses is proposed to depend upon the subunit composition of the receptor. We report a molecular quantification of synaptic AMPA receptors (AMPARs) by employing a single-cell genetic approach coupled with electrophysiology in hippocampal CA1 pyramidal neurons. In contrast to prevailing views, we find that GluA1A2 heteromers are the dominant AMPARs at CA1 cell synapses (∼80%). In cells lacking GluA1, -A2, and -A3, synapses are devoid of AMPARs, yet synaptic NMDA receptors (NMDARs) and dendritic morphology remain unchanged. These data demonstrate a functional dissociation of AMPARs from trafficking of NMDARs and neuronal morphogenesis. This study provides a functional quantification of the subunit composition of AMPARs in the CNS and suggests novel roles for AMPAR subunits in receptor trafficking.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19409270</pmid><doi>10.1016/j.neuron.2009.02.027</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0896-6273 |
| ispartof | Neuron (Cambridge, Mass.), 2009-04, Vol.62 (2), p.254-268 |
| issn | 0896-6273 1097-4199 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3632349 |
| source | MEDLINE; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via ScienceDirect (Elsevier) |
| subjects | Animals Animals, Newborn Biophysics Brain research Electric Stimulation Excitatory Amino Acid Antagonists - pharmacology Excitatory Postsynaptic Potentials - drug effects Excitatory Postsynaptic Potentials - physiology Glutamic Acid - pharmacology Green Fluorescent Proteins - genetics Hippocampus - cytology In Vitro Techniques Membrane Potentials - drug effects Membrane Potentials - genetics Membrane Potentials - physiology Mice Mice, Transgenic Models, Neurological MOLNEURO Neurons Neurons - drug effects Neurons - physiology Patch-Clamp Techniques Polyamines Protein Subunits - genetics Protein Subunits - metabolism Protein Transport - drug effects Receptors, AMPA - deficiency Receptors, AMPA - genetics Receptors, AMPA - metabolism Receptors, Neurotransmitter - genetics Receptors, Neurotransmitter - metabolism Rodents SIGNALING |
| title | Subunit Composition of Synaptic AMPA Receptors Revealed by a Single-Cell Genetic Approach |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-16T18%3A29%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Subunit%20Composition%20of%20Synaptic%20AMPA%20Receptors%20Revealed%20by%20a%20Single-Cell%20Genetic%20Approach&rft.jtitle=Neuron%20(Cambridge,%20Mass.)&rft.au=Lu,%20Wei&rft.date=2009-04-30&rft.volume=62&rft.issue=2&rft.spage=254&rft.epage=268&rft.pages=254-268&rft.issn=0896-6273&rft.eissn=1097-4199&rft_id=info:doi/10.1016/j.neuron.2009.02.027&rft_dat=%3Cproquest_pubme%3E3235467691%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1503774091&rft_id=info:pmid/19409270&rft_els_id=S0896627309002554&rfr_iscdi=true |